Bullous Scabies: Clinical, Dermoscopic, and Pathologic Characteristics of Ten Patients

ABSTRACT.

Bullous scabies (BS) is a rare atypical clinical variant of scabies and is easily confused with bullous disorders. The diagnosis of BS is always a challenge, and physicians often misdiagnose BS patients. Patients with BS admitted from 2012 to 2020 were enrolled in this study. The clinical, dermoscopic, and pathological characteristics of the patients were analyzed retrospectively. Ten patients with BS were enrolled in this study. Seven of the 10 patients were male. The bullae were most commonly found on the thighs and arms (80% of patients). Only 30% of patients (3/10) tested positive for mites and/or eggs by the initial skin scraping, but 100% (5/5) of the patients who received dermoscopy tested positive. Among these 10 patients, only five received a skin biopsy. Subepidermal (4/5) and intraepidermal (1/5) bullae with eosinophil and neutrophil infiltration were observed in five patients. Direct immunofluorescence (DIF) indicated linear deposition of IgG in the basement membrane zone in three patients. Physicians should consider the possibility of BS in patients with blisters, pruritus, and poor response to corticosteroids. Dermoscopy should be prioritized for the differential diagnosis of BS to exclude other bullous disorders. Finally, a biopsy should be performed on each patient with bullae.

INTRODUCTION

Scabies is an infectious skin disease caused by Sarcoptes scabiei (S. scabiei var. hominis) and spreads easily by direct skin-to-skin contact. It is characterized by burrows, papulovesicles, nodules, and intense pruritus at night. Typically, skin lesions are located on the hands, feet, wrists, elbows, back, buttocks and external genitals.¹ Typical scabies is easily identified by the majority of dermatologists. However, some atypical presentations such as eczema, urticaria, pityriasis rosea,² and Darier’s disease³ and various secondary lesions such as folliculitis, eczema, pseudolymphoma, and impetigo, cause difficulties in the diagnosis of scabies.⁴

Bullous scabies (BS), a rare atypical clinical variant of scabies, mainly presents as bullae and crusts and is easily confused with bullous pemphigoid (BP).⁵ To the best of our knowledge, only 28 patients with BS have been reported in the literature available in PubMed over the past 20 years, most of whom were presented as case reports. A serial study is still lacking to date. In the past 8 years, 10 patients were diagnosed with BS at our hospital. Here, we have summarized these 10 cases retrospectively in terms of clinical, dermoscopic, and pathological characteristics.

MATERIALS AND METHODS

A retrospective review of patients seen at the First Affiliated Hospital of Chongqing Medical University in Chongqing, China, was conducted between January 2012 and March 2020. We searched for patients diagnosed with scabies in our electronic medical record system using “scabies” as the keyword, screened the records, and included patients with lesions clinically described as papular and bullous or with blisters. Clinical and dermoscopic data were collected from medical records. Histopathology specimens stained with H&E, if available, were reviewed by a senior dermatopathologist. The Medical Ethics Committee of the First Affiliated Hospital of Chongqing Medical University approved the clinical consent form and research protocol. All patients signed an informed consent form approving the presentation of their clinical pictures with no identifiable information.

Direct immunofluorescence.

Fresh tissue was encased in a frozen slicer with glue, and histological sections (6 µm thick) were mounted on positively charged glass slides. Staining was performed using a single antibody labeled with a fluorophore (FITC). Finally, microscopy with an excitation source at 495 nm was used to image the sections.

Application of 10% sulfur ointment.

Sulfur ointment was applied from the neck down to the whole body once a night for 7–10 days. Bathing and changing clothes was not allowed during the application. After applying the treatment, the patients changed into clean clothing. All patients’ close personal contacts were treated simultaneously to avoid reinfestation. Clothing, bedding, towels, and other items were machine washed (at 50°C or higher).⁶ The patients attended follow-up at least 2 weeks after treatment to evaluate the efficacy of the treatment and to detect recurrence in a timely manner.

RESULTS

A total of 10 patients with BS were identified over the 8-year study period. Seven patients (7/10) were male. The median age of the patients at diagnosis was 49 years (range: 16–81 years). Pruritic skin eruptions were the primary complaint in all cases. Moreover, five patients (5/10) reported that family members or close friends had similar pruritic eruptions. All patients had lesions clinically described as papular and bullous or with blisters more than 5 mm in diameter. Tense bullae with clear fluid or, rarely, hemorrhagic fluid inside always accompanied generalized papules (Figure 1) and pruritus. Erythematous and nodular lesions were reported in eight (8/10) and four (4/10) patients, respectively. The patient demographics and disease characteristics are summarized in Table 1.

Figure 1.

Bullous scabies. (A) Bullae and scabs on the thighs. (B) Bullae and papules on the periumbilicus. (C) Bullae and papules on the left arm. (D) Erythema, papules, scales, and scabs on the lower extremities. This figure appears in color at www.ajtmh.org.

Table 1.

Patient demographics and disease characteristics of 10 patients with bullous scabies

Characteristic	n (of 10)
Gender
Female	3
Male	7
Mean age (years)	50.6
Median (range) age (years)	49 (16–81)
Characteristics
Bullous	10
Papular	10
Pruritic	10
Erythematous	8
Nodular	4
Similar itching skin eruptions in the family	5
Underlying diseases
Hypertension	3
Hyperlipidemia	3
Diabetes	2
Autoimmune disease*	1

^*One patient with systemic lupus erythematosus.

Bullae appeared mainly on the extremities. The thighs and arms were the most common areas involved (8/10), followed by the abdomen (6/10), hands (5/10), legs (5/10), back (4/10), chest (3/10), and other locations (3/10) including the feet, scrotum, and neck. At the time of admission or when reaching a diagnosis was difficult, all patients were examined for scabies by skin scraping (SS). However, positive results were obtained only in three patients (3/10) by the initial SS, and four patients tested positive on the second or subsequent SS examination. In contrast, five patients underwent dermoscopy examination (DS) or DS-guided SS, and all tested positive (5/5). The clinical features are summarized in Table 2.

Table 2.

Clinical features of 10 patients with bullous scabies

No.	Gender	Age	Bullous location	Other types of skin lesions	Infectivity*	Initial SS	DS	BP180/BP230	DIF†	Pathological results	Primary diagnosis	Therapy
1	M	46	Upper limbs, lower limbs, trunk	Multiple erythemas, papules, nodules	Neg	Neg	Pos	Neg/Neg	Neg	Intraepidermal bulla, neutrophils and eosinophils infiltration	Bullous scabies	Sulfur 10% ointment and antihistamines
2	F	69	Bilateral thighs	Erythemas, papules, scab	Neg	Neg	Pos	Neg/Neg	Pos	Subepidermal bulla, a little neutrophils and eosinophils infiltration	Bullous pemphigoid	Sulfur 10% ointment
3	M	47	Buttocks, medial thighs, bilateral palms	Erythemas, vesicles, papules, and plaques	NA	Pos	Pos	NA	NA	NA	Bullous scabies	Sulfur 10% ointment and antihistamines
4	M	81	Dorsal aspects of both feet and hands	Papules, papulovesicles, and nodules	Pos	Pos	Pos	Neg/Neg	NA	NA	Bullous scabies	Sulfur 10% ointment
5	M	29	Hands and lower legs	Papules and nodules	NA	Neg	Pos	Neg/Neg	Pos	Subepidermal blisters, eosinophils, and neutrophils infiltration	Bullous pemphigoid	Sulfur 10% ointment
6‡	M	19	Fingers and palms	Papules and nodules	Pos	Neg	NA	NA	NA	NA	Eczema	Sulfur 10% ointment and antihistamines
7	F	51	Fingers and wrists	Papules, papulovesicles, and nodules	Pos	Pos	NA	NA	NA	NA	Scabies	Sulfur 10% ointment
8‡	M	76	Right abdomen and left thigh	Plaques	Pos	Neg	NA	NA	Pos	Subepidermal bulla, lymphocytes, and eosinophils infiltration in the superficial and deep dermis	Bullous pemphigoid	Sulfur 10% ointment and mupirocin ointment
9‡	M	16	Penile	Nodules, papules, and vesicles	Pos	Neg	NA	NA	NA	NA	Eczema	Sulfur 10% ointment
10‡	F	72	Bilateral thighs	Erythemas, papules, and scab	NA	Neg	NA	NA	Neg	Subepidermal bulla, a small number of neutrophils and eosinophils infiltration	Bullous pemphigoid	Sulfur 10% ointment

DIF = direct immunofluorescence; DS = dermoscopy and dermoscopy guided SS; NA = not available; Neg = negative; Pos = positive; SS = skin scraping.

^*Similar itching skin eruptions in his/her family.

^† Positive results of DIF: linear deposition of IgG in the basement membrane zone.

^‡ Patients were diagnosed with scabies on the second or subsequent skin scraping.

Five patients (5/10) underwent skin biopsies and direct immunofluorescence (DIF) examinations. Histopathological sections were reviewed and are summarized in Table 2. Subepidermal bullae with eosinophil and neutrophil infiltration were seen in four patients (4/5) (Figure 2A and B), and intraepidermal bulla was observed in one patient (1/5) (Figure 2C and D). Three out of five patients were positive on DIF examination, which showed linear deposition of IgG in the basement membrane zone (Figure 2E), and the remaining two patients were negative.

Figure 2.

Histopathology of Bullous scabies. (A) Subepidermal blisters with inflammatory cell infiltration. (B) Inflammatory cells in the subepidermal blister including neutrophils and eosinophils. (C) Intraepidermal blisters and spongiosis with inflammatory cell infiltration. (D) Inflammatory cells in the intraepidermal blister including neutrophils and eosinophils. (E) Direct immunofluorescence results showing linear deposition of IgG in the basement membrane zone. (F) An image of scabies mites on dermoscopy. The dark triangles (black arrow) indicate the mites’ mouthparts. This figure appears in color at www.ajtmh.org.

Before the findings of scabies mites, eggs, or the positive “jet with contrail” sign was observed by dermoscopy (Figure 2F), four patients were misdiagnosed with bullous pemphigoid (4/5) and one was misdiagnosed with eczema (1/5) as a result of the positive results obtained by DIF and the atypical presentation of BS. All five patients responded poorly to treatment with glucocorticoids. After a diagnosis of BS was made, all 10 patients were treated with topical 10% sulfur ointment, leading to rapid improvement of the itching and the gradual disappearance of bullae. No recurrence occurred during 3–6 months of follow-up.

DISCUSSION

Bullous scabies, also called BP-like scabies, is characterized by tense bullae or blisters along with itching, erythematous papules, papulovesicles, or nodules in most cases. Our 10 patients presented with similar characteristics. The patients presented with generalized erythema, papules, intense blisters, and pruritus, however, half of the patients were misdiagnosed with BP or eczema because of the lack of evidence for scabies. These patients responded poorly to glucocorticosteroid treatment. After testing positive for mites by SS or DS, the initiation of antiscabies treatment led to complete recovery. Testing for scabies is critical for the diagnosis of BS and the application of the appropriate therapy.

Bullous scabies usually appears in the elderly, especially in patients over 70 years of age.⁷ Elderly individuals are often in poor physical conditions with a higher possibility of bedridden status or living in nursing homes, which could increase the risk of scabies infection. However, BS also affects many young- and middle-aged individuals, even infants.⁸ Histopathology of blister lesions in BS patients typically shows subepidermal blisters with mixed inflammatory infiltrates, predominantly neutrophils and eosinophils. Among the 10 patients in this study, five underwent DIF, nearly half of whom (3/5) had linear deposition of IgG. Unlike in BP, infiltration of neutrophils can often be observed in the dermis of BS by histological examination. The epidermis can also show different pathological changes, such as spongiosis, intraepidermal blisters, and neutrophil abscesses in the stratum corneum. Occasionally, mite eggs and tunnels can be seen in the stratum corneum, which is helpful for the diagnosis of BS.³

Bullous scabies should be differentiated from bullous disorders,^4,7 especially BP. Of the five misdiagnosed patients in this study, three were misdiagnosed with BP. Bullous scabies and BP share many similar characteristics, such as prevalence in the elderly, tense blisters containing clear fluid, negative Nikolsky’s sign, and subepidermal blister formation with a mixed inflammatory infiltrate predominantly consisting of neutrophils and eosinophils as well as linear depositions of IgG in some patients.^5,9,10 However, many clinical characteristics indicate a higher likelihood of BS. The presence of several skin lesions (e.g., papules, papulovesicles, scales, and blisters) mainly distributed in skin folds or delicate skin areas (e.g., finger web spaces, thigh, abdomen, and male genitalia), pruritus that worsened at night, younger patient ages, poor response to corticosteroid, and similar itchy lesions in the patients’ families or friends were indicative of BS. Moreover, measuring autoantibodies to BP180 and BP230 in the serum is useful for diagnosing BP with high sensitivity (76.1–86.8%) and specificity (85.0–90.5%).^11,12 In this study, the serum of the four patients with available anti-BP180/BP230 data was negative for these autoantibodies, indicating a low probability for BPs.

It is challenging for physicians to distinguish between BS and BP without obtaining a positive test result for mites.¹³ Therefore, it is essential to test for scabies mites in patients with bullous disorders, identifying patients positive for mites contributes to making a timely diagnosis of BS. Skin scraping is a traditional method of testing for mites and has low sensitivity. Dermoscopy, a simple and painless method, has been used for the diagnosis of scabies in recent years. Previous studies revealed that dermoscopy is helpful for diagnosing scabies and has high sensitivity (98.3%) and specificity (97%).^14,15 Of the 10 patients in this study, five underwent dermoscopy tests for scabies, and the positive “jet with contrail” sign was noted in all patients. Therefore, dermoscopy should be a priority for screening patients with suspected scabies. The pathophysiologic mechanisms of bullae formation in patients with BS are still unknown. Several hypotheses have been generated to explain the mechanisms of bullae formation. In DIF-positive patients, mites may cause the exposure and/or alteration of antigens in the basement membrane directly, through the excreted lytic enzymes, or via secretions in feces and saliva, and then induce the production of autoantibodies, which deposit at the dermo-epidermal junction, causing bullae formation.¹⁶ Some common antigenic determinants may exist between mite proteins and antigens in the basement membrane, activating autoimmune reactions and leading to bullae formation.^7,17 In this hypothesis, bullae could be a feature of scabies infestation, and true BP could be caused by scabies in some patients.¹⁸ However, these hypotheses do not explain DIF-negative patients. Autoeczematization may also contribute to bullae formation, which commonly results from infections, skin inflammation, or anaphylaxis.¹⁶ According to this theory, bullae result from skin inflammation or anaphylaxis caused by mites. There are still several phenomena for which there are no reasonable explanations. For instance, BS is rare, while typical scabies is more common, and bullae are more likely to develop in males with scabies.

After the final diagnosis of BS, all the patients improved rapidly after the initiation of antiscabies treatment. Although 10% sulfur ointment is not the most recommended drugs for scabies,¹⁹ it is still widely used in our department because of its cost-effectiveness and safety. Mir F reported that skin lesions in some patients were not sufficiently improved by antiscabies therapy alone but healed well when antiscabies treatment was combined with corticosteroid or immunosuppressive therapies.¹⁸ In these patients, true BP was thought to be caused by scabies infestation, which is usually evaluated using direct or indirect immunofluorescence. Therefore, performing direct and indirect immunofluorescence is recommended for every case of BS.

Some limitations in this study should be noted. First, the main limitation is that DIF was performed in only half of the patients, and the results of serum anti-BP180/BP230 analysis were available for only 40% of the patients. These incomplete data may have led to biased conclusions. Second, we could not obtain the biopsy results from other body regions (from the same person) to determine whether IgG deposition and neutrophil infiltration were systemic or localized. Finally, images of skin lesions, DIF, and histology after treatment were also lacking. These limitations were mainly because of the retrospective nature of this study.

CONCLUSION

Bullous scabies is a rare atypical clinical variant of scabies. Physicians should consider the possibility of BS in patients with pemphigoid-like eruptions, pruritus, and an inadequate response to corticosteroids. Dermoscopy should be prioritized for the differential diagnosis of BS to rule out other bullous disorders. A biopsy/DIF should be performed on each patient with bullae.